The position of selenocysteine in the sequence of amino acids at the active site of qlutathione peroxidase will be determined. The reactions of selenium at the active site will be determined. Reactions to be investigated include oxidation states of selenium and its reduction by glutathione and other sulfhydryl compounds. Using radioisotopes especially 75Se, and isotope dilution and isotope trapping techniques, the metabolic pathway of selenium from dietary seleno-amino acids to selenocysteine in the active site of glutathione peroxidase will be defined. Metabolic controls for this process will be determined. The glutathione peroxidase systems of other organs will be characterized. With the new and sensitive method for determination of in vivo lipid peroxidation via measurement of breath pentane, the effects of dietary selenium will be further defined. The quantitative relationships between components and reactions in the systems involving selenium and glutathione peroxidase will be used in computer simulation models.